Childhood lead poisoning affects some 600,000 children in the United States. Last year, approximately 28,000 children required therapy for an elevated lead burden. Current therapy relies on the use of BAL and CaNa2EDTA, drugs which have a small therapeutic index and are unpleasant to use. 2,3-Dimercaptosuccinic Acid (DMS) is a new, orally effective, non-toxic chelating agent for the treatment of lead and other heavy metal poisonings. Using radioisotopic and biochemical techniques, we propose to study the metabolism, tissse distribution, absorption and excretion of DMS in rats, mice and dogs. The ability of DMS to deplete tissue lead and restore metabolic activity to brain, kidney, liver and the red cell will be determined in rats. The activity of delta-amino-levulinic acid dehydratase (ALA-D) and the tissue concentrations of lead will be measured as functions of DMS dose and time after drug administration. The major objective of this proposal is a clinical trial of DMS in adults and children with lead poisoning. An application for an IND has been submitted to the FDA. Since the last application, we have obtained a supply of purified DMS suitable for clinical use, enabling us to ask for FDA approval. In both adults and children we will monitor the blood lead concentration, erythrocyte ALA-D, urinary and fecal lead excretion, symptoms of lead poisoning, serum clinical chemistries, vital signs, and plasma drug concentration following DMS administration. Cis-dichlorodiammineplatinum II (CPDD) is a new drug which is extremely effective for the treatment of ovarian and testicular cancer. Cumulative renal toxicity, which is similar to the nephropathy of mercury poisoning, is dose-limiting. DMS removes renal platinum deposits in rats which received CPDD. The effect of DMS on cumulative CPDD toxicity will be studied in rats by measuring the urinary excretion of N-acetylglucosaminase (NAG) and leucine aminopeptidase (LAP), new sensitive indices of renal tubular dysfunction.